March, 2002: Minnesota,
U.S.A.
Pokeweed is a common plant that has long been cultivated as an ornamental.
Its fruits have been used to dye cloth and to color wine and candies;
the young shoots and leaves are cooked and eaten as a vegetable. To add
to these economic accolades, an antiviral protein has now been isolated
from transgenic strains of the pokeweed plant. Pokeweed Antiviral Protein
(PAP) has been investigated as a therapy for several types of cancer,
including T-cell leukemia, lymphoma, and Hodgkin disease, as well as for
use against the viruses that cause acquired immune deficiency syndrome
(AIDS).
Nilgun Tumer, an associate professor of plant pathology in the Biotech Center at Cook College, Rutgers University, has been researching PAP and its mechanism for inhibiting viral infection. For the last six years of her research, Professor Turner has collaborated with the Hughes Institute in Minnesota. In 1998, Faith Uckun, president and director of the Hughes Institute, announced that the institute had licensed from Rutgers the exclusive worldwide rights to the transgenic strains of pokeweed for the purpose of continued research.
 Model of a retrovirus. |
An experiment published in the Journal of Virology in 1998 used Saccharomyces cerevisiae, brewer's yeast, to demonstrate how changes in ribosomal frameshifting can inhibit virus propagation. Ribosomal frameshifting is a mechanism retroviruses use to produce additional viral protein. Retroviruses are RNA-containing viruses that convert RNA's genetic material into DNA via reverse transcriptase in order to integrate the host's DNA. Many cancers, as well as the virus that causes AIDS, are retroviruses. In another study, mice were first engineered to have human immune systems and then infected with the HIV virus in order to mimic human AIDS. Amazingly, PAP eradicated the HIV infection in the mice, with no side effects. Based on these and other published findings, the Food and Drug Administration (FDA) in 1998 approved clinical testing of PAP in HIV-infected patients in various treatment centers across the United States. Additionally, the Medicines Control Council in South Africa approved clinical trials for African HIV-infected patients.
 The genetic code for translation. |
 Ribosomal subunits. |
While traditional AIDS therapy attempts to inhibit the functioning of specific AIDS virus components, PAP prevents the units essential for the formation of the virus from being produced in the first place, as indicated by the research done with S. cerevisiae. Specifically, PAP inactivates ribosomes by inhibiting translation. Translation is the process of making a polypeptide from mRNA (messenger RNA, which contains the coding sequence for polypeptides). PAP removes a specific adenine residue from the rRNA (ribosomal RNA, the main ingredient of ribosomes) of the 60S subunit of eukaryotic ribosomes. (Adenine is one of four potential base pairs in RNA; S stands for Svedberg unit, which is used to measure the rate at which a particle suspended in fluid will settle to the bottom when centrifuged.)
Pokeweed, scientifically known as Phytolacca americana, is in the Phytolacaceae family. This family of trees, shrubs, and lianas (woody, climbing vines) is composed of 18 genera and 65 species. Flowers of this family tend to be grouped in showy inflorescences of different types, depending on the specific genus. The alkaloid content is higher in mature leaves than in young leaves; therefore, consuming mature leaves can be fatal. (Alkaloids tend to affect the central nervous system and are often the basis for many pharmaceuticals.) Members of Phytolacaceae are characterized by a deep purple color that is apparent in almost all plant organs. This coloration is caused by betalains, a class of purple pigments that is also responsible for making beets purple.
While research continues on using PAP against retroviruses, studies will also investigate its effectiveness against hepatitis C and the common cold, both viral infections. All parties involved hope the collaborative effort will increase the potential for medical application of PAP.
References, Websites, and Further Reading
Moore, R., W.D. Clark, and D.S. Vodopich. 1998. Botany, 2d ed. New York: McGraw-Hill Companies, pp. 232-41.
Tumer, N.E., et. al. 1998. Pokeweed antiviral protein specifically inhibits Tyl1 directed +1 ribosomal frameshifting and Tyl retrotransposition in Saccharomyces cerevisiae. J. Virology 72, pp. 1036-42.
Zoubenko, O., et al. 1997. Pokeweed antiviral protein activates plant defense pathways independently of salicylic acid and leads to resistance to fungal infection. Nature Biotechnology 15, pp. 992-96.
http://aesop.rutgers.edu/~biotech/faculty/tumer.html
Dr. Nigun Tumor's faculty website at Rutgers Biotech Center
http://www.ces.ncsu.edu/depts/hort/consumer/poison/Phytoam.htm
North Carolina State University, College of Agricultural and Life Sciences,
Phytolacca americana page with photographs
Related Reading in Stern, Kingsley R. 2000. Introductory Plant Biology,
8th ed. New York: McGraw-Hill Companies.
Chapter 2: The Nature of Life
Proteins, polypeptides, and amino acids, pp. 24-26
Nucleic acids, p. 27
Chapter 3: Cells
Ribosomes, p. 41
Chapter 8: Flowers, Fruits, and Seeds
Structure of flowers, pp. 129-32
Inflorescence types, fig. 8.7, p. 131
Chapter 13: Genetics
Structure of DNA, pp. 228-31
RNA and synthesis of proteins, pp. 231-34
Chapter 14: Plant Propagation and Biotechnology
Genetic engineering or recombinant DNA technology, pp. 247-49
Chapter 16: Plant Names and Classification
Genus and species, p. 269
Chapter 17: Kingdom Monera and Viruses
Viruses, pp. 296-301
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